AB0997 New epigenetic predictors of the various localizations osteoarthritis development
Authors: A. Tyurin, R. Khusainova
Journal: Annals of the Rheumatic Diseases (2022)

Background Osteoarthritis (OA) is one of the most common joint diseases, often causing persistent pain and immobilization [1]. The genetic contribution to OA varies from 40% to 65%, depending on the presence of the pathology in the immediate family, the location of the affected joint, sex, and ethnicity of the patients [2]. The study of miRNA target sites is a new promising direction in molecular diagnostics [3]. Objectives The aim of our work was to study the microRNA binding sites of COL1A1, COL11A1, ADAMTS5, MMP1, MMP13, SOX9, GDF5, FGF2, FGFR1, FGFRL1 genes in patients with OA of different localization. Methods A total of 417 women (mean age 51.67±11.5) from Ufa (Republic of Bashkortostan, Russia) participated in the study between January 2013 and August 2017. The patients were examined to diagnose for osteoarthritis according to the criteria of the American College of Rheumatologists (1995) with X-ray confirmation. Overall, 356 women with OA were recruited and divided into 3 groups as follows: subgroup 1 included 84 women affected by generalized OA, subgroup 2 included 197 women affected by knee OA, subgroup 3 included 75 women affected by hip OA. For genotyping, RT-PCR analysis using KASP @ technology was used. Selection of the miRNA target loci was carried out using the database of the National Center for Biotechnological Information ( https://www.ncbi.nlm.nih.gov ), Ensemble Ge-nomeBrowser ( www.ensembl.org ), and the base of polymorphisms of microRNA target sites (http: // compbio. uthsc.edu/miRSNP). As a calculation tool, Statistica v.6.2 (StatSoft) software packages were used. Considering the type I error caused by multiple testing, p values were adjusted by calculating the FDR value using the Benjamini-Hochberg method ( https://tools.carbocation.com/FDR ). Results The T allele of the rs9659030 (COL11A1) was associated with the generalized OA (p = 0.019; OR = 2.0; 95% CI 1.11 to 3.62), the TT genotype was associated with total patients (p = 0.026; OR = 1.59; 95% CI 1.05 to 2.42), generalized OA (p = 0.003; OR = 2.75; 95% CI 1.39 to 5.46) and OA of the hip (p = 0.016; OR = 2.3; 95% CI 1.14 to 4.36). With respect to rs229069 (ADAMTS5), a significant association was found between the C allele and the incidence of total OA (p = 0.018; OR = 1.43; 95% CI 1.06 to 1.93), as well as with the knee OA (p = 0.042; OR = 1.43; 95% CI 1.01 to 2.03) and hip OA (p = 0.026; OR = 2.039; 95% CI 1.08 to 3.85). The CC genotype was also found to be associated with total OA (p = 0.037; OR = 1.53; 95% CI 1.02 to 2.28) and hip OA (p = 0.026; OR = 2.039; 95% CI 1.08 to 3.85). The T allele of rs13317 (FGFR1) was strongly associated with the total OA (p = 0.001; OR = 1.67; 95% CI 1.2 to 2.3), knee OA (p = 0.003; OR = 1.74; 95% CI 1.19 to 2.55) and generalized OA (p = 0.044; OR = 1.67; 95% CI 1.01 to 2.75) After Benjamini-Hochberg correction, rs13317 remained statistically significant in the following groups: the T allele in control vs total patients (adjusted p*= 0.01) and in control vs OA of the knee (adjusted p* = 0.03). Neither the genotype nor the allele frequencies of rs1061347 (COL1A1), rs229077, rs9978597 (ADAMTS5), rs5854, rs470215 (MMP1), rs1042840 (MMP13), rs1042673 (SOX9), rs4647940 (FGFRL1) were significantly different between the affected individuals and normal controls. Conclusion The current study demonstrated an association between the T allele of rs13317 in FGFR1 and incidence of the total OA and knee OA in women from Volga-Ural region of Russia. References [1]Loeser, R., Goldring, S., Scanzello, C. and Goldring, M. (2012). Osteoarthritis: A disease of the joint as an organ. Arthritis &amp; Rheumatism, 64(6), pp.1697-1707. [2]Allen, K. (2010). Racial and ethnic disparities in osteoarthritis phenotypes. Current Opinion in Rheumatology, 22(5), pp.528-532. [3]Zhang, X., Wang, C., Zhao, J., Xu, J., Geng, Y., Dai, L., Huang, Y., Fu, S., Dai, K. and Zhang, X. (2017). miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2. Cell Death &amp; Disease, 8(4), pp.e2734-e2734 Acknowledgements The work was carried out within the framework of the program of activities of the world-class Eurasian Scientific and Educational Center at the expense of subsidies in the field of science from the budget of the Republic of Bashkortostan for state support of young scientists - postgrades and PhD (competition code - SEC-GMU-2021) Disclosure of Interests None declared